The response of a classical Hodgkin–Huxley neuron to an inhibitory input pulse

A population of uncoupled neurons can often be brought close to synchrony by a single strong inhibitory input pulse affecting all neurons equally. This mechanism is thought to underlie some brain rhythms, in particular gamma frequency (30–80 Hz) oscillations in the hippocampus and neocortex. Here we show that synchronization by an inhibitory input pulse often fails for populations of classical Hodgkin–Huxley neurons. Our reasoning suggests that in general, synchronization by inhibitory input pulses can fail when the transition of the target neurons from rest to spiking involves a Hopf bifurcation, especially when inhibition is shunting, not hyperpolarizing. Surprisingly, synchronization is more likely to fail when the inhibitory pulse is stronger or longer-lasting. These findings have potential implications for the question which neurons participate in brain rhythms, in particular in gamma oscillations

Functional properties of neurons derived from in vitro reprogrammed postnatal astroglia

With the exception of astroglia-like cells in the neurogenic niches of the telencephalic subependymal or hippocampal subgranular zone, astroglia in all other regions of the adult mouse brain do not normally generate neurons. Previous studies have shown, however, that early postnatal cortical astroglia in culture can be reprogrammed to adopt a neuronal fate after forced expression of Pax6, a transcription factor (TF) required for proper neuronal specification during embryonic corticogenesis. Here we show that also the proneural genes neurogenin-2 and Mash1 (mammalian achaete schute homolog 1) possess the ability to reprogram astroglial cells from early postnatal cerebral cortex. By means of time-lapse imaging of green fluorescent astroglia, we provide direct evidence that it is indeed cells with astroglial characteristics that give rise to neurons. Using patch-clamp recordings in culture, we show that astroglia-derived neurons acquire active conductances and are capable of firing action potentials, thus displaying hallmarks of true neurons. However, independent of the TF used for reprogramming, astroglia-derived neurons appear to mature more slowly compared with embryonic-born neurons and fail to generate a functional presynaptic output within the culturing period. However, when cocultured with embryonic cortical neurons, astroglia-derived neurons receive synaptic input, demonstrating that they are competent of establishing a functional postsynaptic compartment. Our data demonstrate that single TFs are capable of inducing a remarkable functional reprogramming of astroglia toward a truly neuronal identity

Mitochondrial regulation of local supply of energy in neurons

Brain computation is metabolically expensive and requires the supply of significant amounts of energy. Mitochondria are highly specialized organelles whose main function is to generate cellular energy. Due to their complex morphologies, neurons are especially dependent on a set of tools necessary to regulate mitochondrial function locally in order to match energy provision with local demands. By regulating mitochondrial transport, neurons control the local availability of mitochondrial mass in response to changes in synaptic activity. Neurons also modulate mitochondrial dynamics locally to adjust metabolic efficiency with energetic demand. Additionally, neurons remove inefficient mitochondria through mitophagy. Neurons coordinate these processes through signalling pathways that couple energetic expenditure with energy availability. When these mechanisms fail, neurons can no longer support brain function giving rise to neuropathological states like metabolic syndromes or neurodegeneration

Neural-inspired sensors enable sparse, efficient classification of spatiotemporal data

Sparse sensor placement is a central challenge in the efficient characterization of complex systems when the cost of acquiring and processing data is high. Leading sparse sensing methods typically exploit either spatial or temporal correlations, but rarely both. This work introduces a new sparse sensor optimization that is designed to leverage the rich spatiotemporal coherence exhibited by many systems. Our approach is inspired by the remarkable performance of flying insects, which use a few embedded strain-sensitive neurons to achieve rapid and robust flight control despite large gust disturbances. Specifically, we draw on nature to identify targeted neural-inspired sensors on a flapping wing to detect body rotation. This task is particularly challenging as the rotational twisting mode is three orders-of-magnitude smaller than the flapping modes. We show that nonlinear filtering in time, built to mimic strain-sensitive neurons, is essential to detect rotation, whereas instantaneous measurements fail. Optimized sparse sensor placement results in efficient classification with approximately ten sensors, achieving the same accuracy and noise robustness as full measurements consisting of hundreds of sensors. Sparse sensing with neural inspired encoding establishes a new paradigm in hyper-efficient, embodied sensing of spatiotemporal data and sheds light on principles of biological sensing for agile flight control.Comment: 21 pages, 19 figure

Cortical Overexpression of Neuronal Calcium Sensor-1 Induces Functional Plasticity in Spinal Cord Following Unilateral Pyramidal Tract Injury in Rat

Following trauma of the adult brain or spinal cord the injured axons of central neurons fail to regenerate or if intact display only limited anatomical plasticity through sprouting. Adult cortical neurons forming the corticospinal tract (CST) normally have low levels of the neuronal calcium sensor-1 (NCS1) protein. In primary cultured adult cortical neurons, the lentivector-induced overexpression of NCS1 induces neurite sprouting associated with increased phospho-Akt levels. When the PI3K/Akt signalling pathway was pharmacologically inhibited the NCS1-induced neurite sprouting was abolished. The overexpression of NCS1 in uninjured corticospinal neurons exhibited axonal sprouting across the midline into the CST-denervated side of the spinal cord following unilateral pyramidotomy. Improved forelimb function was demonstrated behaviourally and electrophysiologically. In injured corticospinal neurons, overexpression of NCS1 induced axonal sprouting and regeneration and also neuroprotection. These findings demonstrate that increasing the levels of intracellular NCS1 in injured and uninjured central neurons enhances their intrinsic anatomical plasticity within the injured adult central nervous system

Death Commitment Point Is Advanced by Axotomy in Sympathetic Neurons

Axotomized neurons have several characteristics that are different from intact neurons. Here we show that, unlike established cultures, the axotomized sympathetic neurons deprived of NGF become committed to die before caspase activation, since the same proportion of NGF-deprived neurons are rescued by NGF regardless of whether caspases are inhibited by the pan-caspase inhibitor Boc-Asp(O-methyl)-CH2F (BAF). Despite prolonged Akt and ERK signaling induced by NGF after BAF treatment has prevented death, the neurons fail to increase protein synthesis, recover ATP levels, or grow. Within 3 d, all the mitochondria disappear without apparent removal of any other organelles or loss of membrane integrity. Although NGF does rescue intact BAF-treated 6-d cultures after NGF deprivation, rescue by NGF fails when these neurons are axotomized before NGF deprivation and BAF treatment. Moreover, cytosolic cytochrome c rapidly kills axotomized neurons. We propose that axotomy induces signals that make sympathetic neurons competent to die prematurely. NGF cannot repair these NGF-deprived, BAF-treated neurons because receptor signaling (which is normal) is uncoupled from protein renewal, and the mitochondria (which are damaged) go on to be eliminated. Hence, the order of steps underlying neuronal death commitment is mutable and open to regulation

Graded potential of neural crest to form cornea, sensory neurons and cartilage along the rostrocaudal axis

Neural crest cells arising from different rostrocaudal axial levels form different sets of derivatives as diverse as ganglia, cartilage and cornea. These variations may be due to intrinsic properties of the cell populations, different environmental factors encountered during migration or some combination thereof. We test the relative roles of intrinsic versus extrinsic factors by challenging the developmental potential of cardiac and trunk neural crest cells via transplantation into an ectopic midbrain environment. We then assess long-term survival and differentiation into diverse derivatives, including cornea, trigeminal ganglion and branchial arch cartilage. Despite their ability to migrate to the periocular region, neither cardiac nor trunk neural crest contribute appropriately to the cornea, with cardiac crest cells often forming ectopic masses on the corneal surface. Similarly, the potential of trunk and cardiac neural crest to form somatosensory neurons in the trigeminal ganglion was significantly reduced compared with control midbrain grafts. Cardiac neural crest exhibited a reduced capacity to form cartilage, contributing only nominally to Meckle's cartilage, whereas trunk neural crest formed no cartilage after transplantation, even when grafted directly into the first branchial arch. These results suggest that neural crest cells along the rostrocaudal axis display a graded loss in developmental potential to form somatosensory neurons and cartilage even after transplantation to a permissive environment. Hox gene expression was transiently maintained in the cardiac neural tube and neural crest at 12 hours post-transplantation to the midbrain, but was subsequently downregulated. This suggests that long-term differences in Hox gene expression cannot account for rostrocaudal differences in developmental potential of neural crest populations in this case